This proposal addresses the general method of preparation of linear and nonlinear triquinane serquiterpanes, in particular several biologically active coriolins and hirsuitic acids. Our proposed syntheses represent newly redesigned versions of the original research propositions funded in 1981. The new approach is perhaps more flexible in the ultimate obtention of the natural products for medicinal screening. The continuous supply of especially the antitumor and antibiotic coriolins from natural sources seems uncertain and, therefore, it is essential that an efficient and a general preparation of these compounds be available. Our synthetic plan thus focuses on the rapid production of a flexible tricyclic intermediate which is equipped with properly differentiated functionalities to permit its conversion into various coriolin natural products. This intermediate is accessible through the application of intramolecular cyclopentene annulation methodology which has been developed in our laboratory and pursued in conjunction with terpene synethesis. Following our recent work on the synthesis if triquinanes we propose to concentrate our efforts on the specific aims summarized below: a. Synthesis of five coriolins and three hirsutic acids by a redesigned strategy. b. Synthesis of other linear and nonlinear triquinanes of medicinal interest by an extension of our methodology. c. Investigation of the ulity of the intramolecular Simmons-Smith reaction and sequential radical alkylation of dienic dihalides as alternatives to methods utilizing diazoketones for cyclopropanations and d. Explorations of some newly discovered aspects of the Reformatsky reaction of halocrotonates in organic synthesis. The overall significance of the proposed research lies not only in the provision of the biologically important target compounds but also in the development of what appears to be a quite general system-oriented design of cyclopentanoid terpenes. The pursuit of the novel application of the two established reactions will enrich the compendium of the methods available for the carbon-carrbon bond formation. The budgetary period of this applications has been expanded to five years in order to further utilize the Cyclopentene Annualtion Methodology in the synthesis of biologically active cyclopentanoid terpenes and to begin detailed investigations of several new and potentially general synthetic methods.